blocking myofibroblast differentiation with an anti-tgfβ...
TRANSCRIPT
Blocking myofibroblast differentiation with an anti-TGFβ antibody decreases the induction of higher-order aberrations after photorefractive keratectomy (PRK) in a cat model
Bühren J, Nagy LJ, DiMagistris M, MacRae SM, Huxlin KR
Advanced Physiological Optics Laboratory Department of Ophthalmology University of Rochester Medical Center Rochester, N.Y., USA
Objective
• Wound healing effects can compromise the outcome of surface ablation procedures (PRK)
• TGFβ (Transforming Growth Factor β) plays a pivotal role in corneal wound healing (esp. transformation of keratocytes into myofibroblasts)
Objective
• Wound healing effects can compromise the outcome of surface ablation procedures (PRK)
• TGFβ (Transforming Growth Factor β) plays a pivotal role in corneal wound healing (myofibroblast transformation)
• Hypothesis: “Contractile myofibroblasts contribute to induction of higher order optical aberrations after PRK”
Methods: PRK in cats
• 8 eyes from 5 domestic shorthair cats (felis cattus) underwent PRK for myopia (Planoscan, B & L) -10 D, 6mm OZ
• follow-up exams: 2, 4, 8 and 12 weeks
treatment eye: anti-TGFβ
(1mg/mL b.i.d.)
control eye: vehicle solution b.i.d.
for 7 days
Methods: aberrometry in awake-behaving cats
• wavefront sensing (H/S sensor - 300µm lenslet spacing) in fixating cats • Zernike decomposition (10th order)
– LOA RMS, coma RMS, SA RMS, residual RMS – VSOTF
Huxlin, Yoon, Nagy, Porter, Williams. Vis Res 2004;44:2159-69 Nagy, MacRae, Yoon, Cox, Huxlin , J Cat Refr Surg 2007; 33: 1051-1064 Bühren, Yoon, Kenner, MacRae, Huxlin, IOVS 2007; 48: 5806 – 5814
1 mm
Results: wavefront I (LOA)
M [D
]
time [week] 0 4 8 12
-2
0
2
4
6
8 M
J0 [D
]
time [week] 0 4 8 12
-1.0
-0.5
0
0.5
1.0 J0
J45
[D]
time [week] 0 4 8 12
-1.0
-0.5
0
0.5
1.0
J45
treatments controls
LOA: no differences
Results: wavefront II (HOA)
coma
time [week] 0 4 8 12
com
a R
MS
[µm
]
0
0.5
1.0
1.5
time [week] 0 4 8 12
SA
RM
S [µ
m] spherical
0
0.5
1.0
1.5
time [week] 0 4 8 12
resi
dual
HO
A R
MS
[µm
]
0
0.5
1.0
1.5 residual
treatments controls
C ≥2
n
C ±1
n C 0
n
Results: wavefront II (HOA)
coma
time [week] 0 4 8 12
com
a R
MS
[µm
]
0
0.5
1.0
1.5
time [week] 0 4 8 12
SA
RM
S [µ
m] spherical
0
0.5
1.0
1.5
time [week] 0 4 8 12
resi
dual
HO
A R
MS
[µm
] 0
0.5
1.0
1.5
residual
log
BC
VS
OTF
-2.0
-1.6
-1.2
-0.8
-0.4
0 BCVSOTF
time [week] 0 4 8 12
treatments controls
α-TGF treatment group: • less coma, SA and other HOA
• better retinal image quality • less fluctuation
treatments controls